CD133 suppression increases the sensitivity of prostate cancer cells to paclitaxel

Molecular Biology Reports - One of the major barriers in cancer therapy is the resistance to conventional therapies and cancer stem cells (CSCs) are among the main causes of this problem. CD133 as...     

Synthetic biology in various cellular and molecular fields: applications,limitations, and perspective

Molecular Biology Reports - Synthetic biology breakthroughs have facilitated genetic circuit engineering to program cells through novel biological functions, dynamic gene expressions, as well as...     

Modulation of Apoptosis and Oxidative Stress with Nesfatin-1 in Doxorubicin Induced Cardiotoxicity in Male Rat

International Journal of Peptide Research and Therapeutics - Fibroblast growth factor 21 (FGF21) is a metabolic regulator with a wide range of biological functions. Although previous studies have...     

Prediction of 492 human protein kinase substrate specificities

Background

Complex intracellular signaling networks monitor diverse environmental inputs to evoke appropriate and coordinated effector responses. Defective signal transduction underlies many pathologies, including cancer, diabetes, autoimmunity and about 400 other human diseases. Therefore, there is high impetus to define the composition and architecture of cellular communications networks in humans. The major components of intracellular signaling networks are protein kinases and protein phosphatases, which catalyze the reversible phosphorylation of proteins. Here, we have focused on identification of kinase-substrate interactions through prediction of the phosphorylation site specificity from knowledge of the primary amino acid sequence of the catalytic domain of each kinase.

Results

The presented method predicts 488 different kinase catalytic domain substrate specificity matrices in 478 typical and 4 atypical human kinases that rely on both positive and negative determinants for scoring individual phosphosites for their suitability as kinase substrates. This represents a marked advancement over existing methods such as those used in NetPhorest (179 kinases in 76 groups) and NetworKIN (123 kinases), which consider only positive determinants for kinase substrate prediction. Comparison of our predicted matrices with experimentally-derived matrices from about 9,000 known kinase-phosphosite substrate pairs revealed a high degree of concordance with the established preferences of about 150 well studied protein kinases. Furthermore for many of the better known kinases, the predicted optimal phosphosite sequences were more accurate than the consensus phosphosite sequences inferred by simple alignment of the phosphosites of known kinase substrates.

Conclusions

Application of this improved kinase substrate prediction algorithm to the primary structures of over 23, 000 proteins encoded by the human genome has permitted the identification of about 650, 000 putative phosphosites, which are posted on the open source PhosphoNET website (http://www.phosphonet.ca).

     

Synthesis, crystal structure, magnetic and redox properties of copper(II) complexes of N-alkyl(aryl) tBu-salicylaldimines

A series of novel copper(II) complexes, L₂Cu with newly synthesized 3,5--salicylaldimine (or 5--salicylaldimine) ligands derived from 2,4-di-tert-butyl phenol (or 4-tert-butyl phenol) and alkyl (aryl) amines have been prepared and their spectroscopic (IR, UV-Vis, ESI-MS), X-ray, magnetic and redox properties have been investigated. The X-ray crystallography analysis shows that all complexes are monomeric and their copper(II) centers are surrounded by phenolate oxygens and imine nitrogen atoms. Therefore, the coordination sphere around the copper atoms is N₂O₂ as seen in galactose oxidase active site. In addition, the geometric configurations of all complexes are square planar or slightly distorted square planar. The crystal system for all complexes is monoclinic, except for which is orthorhombic. The temperature dependence of magnetic susceptibility of complexes confirms the mononuclear structure of complexes. Oxidation of the Cu(II) complexes yielded the corresponding Cu(II)-phenoxyl radical species during the cyclic voltammetry experiments.     

Analysis of beta-hemolysis in human blood agars by Streptococcus pyogenes

The aim of the study was to assess the reliability of human blood agar media (HuBA) in identifying Streptococcus pyogenes by hemolysis analysis. We analyze several factors that might affect the accuracy of HuBA media for microbial analysis, including incubation time, blood group, Rh factor and presence of antistreptolysin-o.     

The role of copper transporters in the development of resistance to Pt drugs

Recent studies in yeast, mouse and human cells suggest that the conserved metal binding transporters of the Cu homeostasis pathway can mediate resistance to Pt drugs in cancer cells. This review summarizes the data available from these studies. The observation that cells selected for resistance to Cu or the Pt drugs display bidirectional cross-resistance, parallel defects in the transport of Cu and the Pt drugs and altered expression of Cu transporters is consistent with the concept that the Cu homeostasis proteins regulate sensitivity to the Pt drugs by influencing their uptake, efflux and intracellular distribution. This model is supported by the finding that when mammalian and yeast cells are genetically engineered to express altered levels of the Cu transporters they exhibit altered sensitivity to Pt drugs and are defective in intracellular Pt accumulation due to altered uptake and/or efflux rates. Negative associations between the expression of ATP7A and ATP7B and the outcome of Pt therapy further support the significance of the Cu homeostasis proteins as both markers of and contributors to Pt resistance.